Skip to main content
Erschienen in:

01.11.2009 | CME Weiterbildung · Zertifizierte Fortbildung

Methotrexat in der Rheumatologie

verfasst von: Prof. Dr. C. Fiehn

Erschienen in: Zeitschrift für Rheumatologie | Ausgabe 9/2009

Einloggen, um Zugang zu erhalten

Zusammenfassung

Der Folsäureantagonist Methotrexat (MTX) hat über die letzten Jahrzehnte insbesondere in der Therapie der rheumatoiden Arthritis (RA) eine überragende Rolle erlangt. MTX ist bei der RA nicht nur Disease Modifying Anti-Rheumatic Drug der ersten Wahl, eine Vielzahl von randomisierten klinischen Studien zeigt darüber hinaus, dass es auch ein notwendiger Kombinationspartner ist, um eine optimale Wirkung von Biologika zu erreichen. MTX ist daher der zentrale Pfeiler der medikamentösen Therapie der RA. Alle Untersuchungen haben immer wieder die gute Sicherheit des Medikaments auch bei Langzeiteinnahme belegt. In weiteren Indikationen der Rheumatologie hat sich MTX fest etabliert. Die Wirkungsweise von MTX in der Entzündung ist komplex, wird aber zunehmend besser verstanden. Erste Ansätze zur Vorhersage der Wirkung und Verträglichkeit von MTX mit Hilfe der Analyse von genetischen Polymorphismen wurden beschrieben. MTX-Konjugate, welche endogenes Albumin als Trägermolekül in die Synovitis nutzen, wie auch neue rezeptorspezifische Folatantagonisten sind derzeit in präklinischer Testung. Das Ziel, das besonders erfolgreiche Therapieprinzip der Folatinhibition in der Behandlung rheumatischer Erkrankungen für die Zukunft weiterzuentwickeln, scheint erreichbar.
Literatur
1.
Zurück zum Zitat Alarcon GS, Kremer JM, Macaluso M et al (1997) Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med 127:356–364PubMed Alarcon GS, Kremer JM, Macaluso M et al (1997) Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group. Ann Intern Med 127:356–364PubMed
2.
Zurück zum Zitat Andersen PA, West SG, O’Dell JR et al (1985) Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann Intern Med 103:489–496PubMed Andersen PA, West SG, O’Dell JR et al (1985) Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann Intern Med 103:489–496PubMed
3.
Zurück zum Zitat Anderson JJ, Wells G, Verhoeven AC, Felson DT (2000) Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 43:22–29CrossRefPubMed Anderson JJ, Wells G, Verhoeven AC, Felson DT (2000) Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 43:22–29CrossRefPubMed
4.
Zurück zum Zitat Baecklund E, Askling J, Rosenquist R et al (2004) Rheumatoid arthritis and malignant lymphomas. Curr Opin Rheumatol 16:254–261CrossRefPubMed Baecklund E, Askling J, Rosenquist R et al (2004) Rheumatoid arthritis and malignant lymphomas. Curr Opin Rheumatol 16:254–261CrossRefPubMed
5.
Zurück zum Zitat Ballantyne FC, Fleck A, Dick WC (1971) Albumin metabolism in rheumatoid arthritis. Ann Rheum Dis 30:265–270CrossRefPubMed Ballantyne FC, Fleck A, Dick WC (1971) Albumin metabolism in rheumatoid arthritis. Ann Rheum Dis 30:265–270CrossRefPubMed
6.
Zurück zum Zitat Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J (1996) Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin Pharmacokinet 30:194–210CrossRefPubMed Bannwarth B, Pehourcq F, Schaeverbeke T, Dehais J (1996) Clinical pharmacokinetics of low-dose pulse methotrexate in rheumatoid arthritis. Clin Pharmacokinet 30:194–210CrossRefPubMed
7.
Zurück zum Zitat Bathon JM, Genovese MC (2003) The Early Rheumatoid Arthritis (ERA) trial comparing the efficacy and safety of etanercept and methotrexate. Clin Exp Rheumatol 21 (Suppl 31):S195–S197PubMed Bathon JM, Genovese MC (2003) The Early Rheumatoid Arthritis (ERA) trial comparing the efficacy and safety of etanercept and methotrexate. Clin Exp Rheumatol 21 (Suppl 31):S195–S197PubMed
8.
Zurück zum Zitat Black RL, O’Brian RL, Vanscott EJ et al (1964) methotrexate therapy in psoriatic arthritis; double blind study on 21 patients. JAMA 189:743–747PubMed Black RL, O’Brian RL, Vanscott EJ et al (1964) methotrexate therapy in psoriatic arthritis; double blind study on 21 patients. JAMA 189:743–747PubMed
9.
Zurück zum Zitat Braun J, Kastner P, Flaxenberg P et al (2008) Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum 58:73–81CrossRefPubMed Braun J, Kastner P, Flaxenberg P et al (2008) Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial. Arthritis Rheum 58:73–81CrossRefPubMed
10.
11.
Zurück zum Zitat Breedveld FC, Weisman MH, Kavanaugh AF et al (2006) The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 54:26–37CrossRefPubMed Breedveld FC, Weisman MH, Kavanaugh AF et al (2006) The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum 54:26–37CrossRefPubMed
12.
Zurück zum Zitat Caporali R, Cimmino MA, Ferraccioli G et al (2004) Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 141:493–500PubMed Caporali R, Cimmino MA, Ferraccioli G et al (2004) Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 141:493–500PubMed
13.
Zurück zum Zitat Carneiro JR, Sato EI (1999) Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus. J Rheumatol 26:1275–1279PubMed Carneiro JR, Sato EI (1999) Double blind, randomized, placebo controlled clinical trial of methotrexate in systemic lupus erythematosus. J Rheumatol 26:1275–1279PubMed
14.
Zurück zum Zitat Chen J, Liu C, Lin J (2006) Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev CD004524 Chen J, Liu C, Lin J (2006) Methotrexate for ankylosing spondylitis. Cochrane Database Syst Rev CD004524
15.
Zurück zum Zitat Choi HK, Hernan MA, Seeger JD et al (2002) Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 359:1173–1177CrossRefPubMed Choi HK, Hernan MA, Seeger JD et al (2002) Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study. Lancet 359:1173–1177CrossRefPubMed
16.
Zurück zum Zitat Combe B, Landewe R, Lukas C et al (2007) EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 66:34–45CrossRefPubMed Combe B, Landewe R, Lukas C et al (2007) EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 66:34–45CrossRefPubMed
17.
Zurück zum Zitat Cronstein BN, Eberle MA, Gruber HE, Levin RI (1991) Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci U S A 88:2441–2445CrossRefPubMed Cronstein BN, Eberle MA, Gruber HE, Levin RI (1991) Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci U S A 88:2441–2445CrossRefPubMed
18.
Zurück zum Zitat Cutolo M, Sulli A, Pizzorni C et al (2001) Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis 60:729–735CrossRefPubMed Cutolo M, Sulli A, Pizzorni C et al (2001) Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis. Ann Rheum Dis 60:729–735CrossRefPubMed
19.
Zurück zum Zitat Dalrymple JM, Stamp LK, O’Donnell JL et al (2008) Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 58:3299–3308CrossRefPubMed Dalrymple JM, Stamp LK, O’Donnell JL et al (2008) Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis. Arthritis Rheum 58:3299–3308CrossRefPubMed
20.
Zurück zum Zitat de GK, Rasmussen N, Bacon PA et al (2005) Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 52:2461–2469CrossRef de GK, Rasmussen N, Bacon PA et al (2005) Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum 52:2461–2469CrossRef
21.
Zurück zum Zitat de GK, Reinhold-Keller E, Tatsis E et al (1996) Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis. Methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum 39:2052–2061CrossRef de GK, Reinhold-Keller E, Tatsis E et al (1996) Therapy for the maintenance of remission in sixty-five patients with generalized Wegener’s granulomatosis. Methotrexate versus trimethoprim/sulfamethoxazole. Arthritis Rheum 39:2052–2061CrossRef
22.
Zurück zum Zitat Dervieux T, Furst D, Lein DO et al (2004) Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 50:2766–2774CrossRefPubMed Dervieux T, Furst D, Lein DO et al (2004) Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum 50:2766–2774CrossRefPubMed
23.
Zurück zum Zitat Dervieux T, Furst D, Lein DO et al (2005) Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 64:1180–1185CrossRefPubMed Dervieux T, Furst D, Lein DO et al (2005) Pharmacogenetic and metabolite measurements are associated with clinical status in patients with rheumatoid arthritis treated with methotrexate: results of a multicentred cross sectional observational study. Ann Rheum Dis 64:1180–1185CrossRefPubMed
24.
Zurück zum Zitat Elnakat H, Ratnam M (2004) Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy. Adv Drug Deliv Rev 56:1067–1084CrossRefPubMed Elnakat H, Ratnam M (2004) Distribution, functionality and gene regulation of folate receptor isoforms: implications in targeted therapy. Adv Drug Deliv Rev 56:1067–1084CrossRefPubMed
25.
Zurück zum Zitat Emery P, Breedveld FC, Hall S et al (2008) Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 372:375–382CrossRefPubMed Emery P, Breedveld FC, Hall S et al (2008) Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet 372:375–382CrossRefPubMed
26.
Zurück zum Zitat Fiehn C (2009) The future of folic acid antagonist therapy in rheumatoid arthritis. Arthritis Rheum 60:1–4CrossRefPubMed Fiehn C (2009) The future of folic acid antagonist therapy in rheumatoid arthritis. Arthritis Rheum 60:1–4CrossRefPubMed
27.
Zurück zum Zitat Fiehn C, Kratz F, Sass G et al (2008) Targeted drug delivery by in vivo coupling to endogenous albumin: an albumin-binding prodrug of methotrexate (MTX) is better than MTX in the treatment of murine collagen-induced arthritis. Ann Rheum Dis 67:1188–1191CrossRefPubMed Fiehn C, Kratz F, Sass G et al (2008) Targeted drug delivery by in vivo coupling to endogenous albumin: an albumin-binding prodrug of methotrexate (MTX) is better than MTX in the treatment of murine collagen-induced arthritis. Ann Rheum Dis 67:1188–1191CrossRefPubMed
28.
Zurück zum Zitat Fiehn C, Muller-Ladner U, Gay S et al (2004) Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX. Rheumatology (Oxford) 43:1097–1105 Fiehn C, Muller-Ladner U, Gay S et al (2004) Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX. Rheumatology (Oxford) 43:1097–1105
29.
Zurück zum Zitat Fiehn C, Neumann E, Wunder A et al (2004) Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress synovial fibroblast invasion and cartilage degradation in vivo. Ann Rheum Dis 63:884–886CrossRefPubMed Fiehn C, Neumann E, Wunder A et al (2004) Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress synovial fibroblast invasion and cartilage degradation in vivo. Ann Rheum Dis 63:884–886CrossRefPubMed
30.
Zurück zum Zitat Fiehn C, Wunder A, Krienke S et al (2005) Lack of evidence for inhibition of angiogenesis as a central mechanism of the antiarthritic effect of methotrexate. Rheumatol Int 25:108–113CrossRefPubMed Fiehn C, Wunder A, Krienke S et al (2005) Lack of evidence for inhibition of angiogenesis as a central mechanism of the antiarthritic effect of methotrexate. Rheumatol Int 25:108–113CrossRefPubMed
31.
Zurück zum Zitat Fortin PR, Abrahamowicz M, Ferland D et al (2008) Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 59:1796–1804CrossRefPubMed Fortin PR, Abrahamowicz M, Ferland D et al (2008) Steroid-sparing effects of methotrexate in systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 59:1796–1804CrossRefPubMed
32.
Zurück zum Zitat Gaffo AL, Alarcon GS (2008) Methotrexate is not associated with progression of interstitial lung disease in rheumatoid arthritis. Arch Intern Med 168:1927–1928CrossRefPubMed Gaffo AL, Alarcon GS (2008) Methotrexate is not associated with progression of interstitial lung disease in rheumatoid arthritis. Arch Intern Med 168:1927–1928CrossRefPubMed
33.
Zurück zum Zitat Haibel H, Brandt HC, Song IH et al (2007) No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis 66:419–421CrossRefPubMed Haibel H, Brandt HC, Song IH et al (2007) No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial. Ann Rheum Dis 66:419–421CrossRefPubMed
34.
Zurück zum Zitat Heijstek MW, Wulffraat NM, Kuis W et al (2009) A combined clinical and pharmacogenetic model to predict methotrexate efficacy in juvenile idiopathic arthritis. Ann Rheum Dis 68 (Suppl3):S169CrossRef Heijstek MW, Wulffraat NM, Kuis W et al (2009) A combined clinical and pharmacogenetic model to predict methotrexate efficacy in juvenile idiopathic arthritis. Ann Rheum Dis 68 (Suppl3):S169CrossRef
35.
Zurück zum Zitat Hoekstra M, van de Laar MA, Bernelot Moens HJ et al (2003) Longterm observational study of methotrexate use in a Dutch cohort of 1022 patients with rheumatoid arthritis. J Rheumatol 30:2325–2329PubMed Hoekstra M, van de Laar MA, Bernelot Moens HJ et al (2003) Longterm observational study of methotrexate use in a Dutch cohort of 1022 patients with rheumatoid arthritis. J Rheumatol 30:2325–2329PubMed
36.
Zurück zum Zitat Hoffman GS, Cid MC, Hellmann DB et al (2002) A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum 46:1309–1318CrossRefPubMed Hoffman GS, Cid MC, Hellmann DB et al (2002) A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum 46:1309–1318CrossRefPubMed
37.
Zurück zum Zitat Hoffman GS, Leavitt RY, Kerr GS et al (1994) Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum 37:578–582CrossRefPubMed Hoffman GS, Leavitt RY, Kerr GS et al (1994) Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum 37:578–582CrossRefPubMed
38.
Zurück zum Zitat Jeurissen ME, Boerbooms AM, van de Putte LB et al (1991) Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis. A randomized, double-blind study. Ann Intern Med 114:999–1004PubMed Jeurissen ME, Boerbooms AM, van de Putte LB et al (1991) Influence of methotrexate and azathioprine on radiologic progression in rheumatoid arthritis. A randomized, double-blind study. Ann Intern Med 114:999–1004PubMed
39.
Zurück zum Zitat Jover JA, Hernandez-Garcia C, Morado IC et al (2001) Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized, double-blind, placebo-controlled trial. Ann Intern Med 134:106–114PubMed Jover JA, Hernandez-Garcia C, Morado IC et al (2001) Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized, double-blind, placebo-controlled trial. Ann Intern Med 134:106–114PubMed
40.
Zurück zum Zitat Katchamart W, Trudeau J, Phumethum V, Bombardier C (2009) Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 68:1105–1112CrossRefPubMed Katchamart W, Trudeau J, Phumethum V, Bombardier C (2009) Efficacy and toxicity of methotrexate (MTX) monotherapy versus MTX combination therapy with non-biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and meta-analysis. Ann Rheum Dis 68:1105–1112CrossRefPubMed
41.
Zurück zum Zitat Klareskog L, van der HD, de Jager JP et al (2004) Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363:675–681CrossRefPubMed Klareskog L, van der HD, de Jager JP et al (2004) Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363:675–681CrossRefPubMed
42.
Zurück zum Zitat Krause D, Schleusser B, Herborn G, Rau R (2000) Response to methotrexate treatment is associated with reduced mortality in patients with severe rheumatoid arthritis. Arthritis Rheum 43:14–21CrossRefPubMed Krause D, Schleusser B, Herborn G, Rau R (2000) Response to methotrexate treatment is associated with reduced mortality in patients with severe rheumatoid arthritis. Arthritis Rheum 43:14–21CrossRefPubMed
43.
Zurück zum Zitat Kremer JM (2004) Toward a better understanding of methotrexate. Arthritis Rheum 50:1370–1382CrossRefPubMed Kremer JM (2004) Toward a better understanding of methotrexate. Arthritis Rheum 50:1370–1382CrossRefPubMed
44.
Zurück zum Zitat Kremer JM (2004) Toward a better understanding of methotrexate. Arthritis Rheum 50:1370–1382CrossRefPubMed Kremer JM (2004) Toward a better understanding of methotrexate. Arthritis Rheum 50:1370–1382CrossRefPubMed
45.
Zurück zum Zitat Kremer JM (2008) Methotrexate treatment of rheumatic diseases: can we do better? Arthritis Rheum 58:3279–3282CrossRefPubMed Kremer JM (2008) Methotrexate treatment of rheumatic diseases: can we do better? Arthritis Rheum 58:3279–3282CrossRefPubMed
46.
Zurück zum Zitat Kremer JM, Genovese MC, Cannon GW et al (2002) Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 137:726–733PubMed Kremer JM, Genovese MC, Cannon GW et al (2002) Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 137:726–733PubMed
47.
Zurück zum Zitat Lafforgue P, Monjanel-Mouterde S, Durand A et al (1995) Lack of correlation between pharmacokinetics and efficacy of low dose methotrexate in patients with rheumatoid arthritis. J Rheumatol 22:844–849PubMed Lafforgue P, Monjanel-Mouterde S, Durand A et al (1995) Lack of correlation between pharmacokinetics and efficacy of low dose methotrexate in patients with rheumatoid arthritis. J Rheumatol 22:844–849PubMed
48.
Zurück zum Zitat Levick JR (1981) Permeability of rheumatoid and normal human synovium to specific plasma proteins. Arthritis Rheum 24:1550–1560CrossRefPubMed Levick JR (1981) Permeability of rheumatoid and normal human synovium to specific plasma proteins. Arthritis Rheum 24:1550–1560CrossRefPubMed
49.
Zurück zum Zitat Mahr AD, Jover JA, Spiera RF et al (2007) Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 56:2789–2797CrossRefPubMed Mahr AD, Jover JA, Spiera RF et al (2007) Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum 56:2789–2797CrossRefPubMed
50.
Zurück zum Zitat Nakashima-Matsushita N, Homma T, Yu S et al (1999) Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis Rheum 42:1609–1616CrossRefPubMed Nakashima-Matsushita N, Homma T, Yu S et al (1999) Selective expression of folate receptor beta and its possible role in methotrexate transport in synovial macrophages from patients with rheumatoid arthritis. Arthritis Rheum 42:1609–1616CrossRefPubMed
51.
Zurück zum Zitat Niehues T, Horneff G, Michels H et al (2004) Evidenzbasierter Einsatz von Methotrexat bei Kindern mit rheumatischen Erkrankungen. Z Rheumatol 63:147–158CrossRefPubMed Niehues T, Horneff G, Michels H et al (2004) Evidenzbasierter Einsatz von Methotrexat bei Kindern mit rheumatischen Erkrankungen. Z Rheumatol 63:147–158CrossRefPubMed
52.
Zurück zum Zitat Nordstrom DM, West SG, Andersen PA, Sharp JT (1987) Pulse methotrexate therapy in rheumatoid arthritis. A controlled prospective roentgenographic study. Ann Intern Med 107:797–801PubMed Nordstrom DM, West SG, Andersen PA, Sharp JT (1987) Pulse methotrexate therapy in rheumatoid arthritis. A controlled prospective roentgenographic study. Ann Intern Med 107:797–801PubMed
53.
Zurück zum Zitat O’Dell JR, Haire CE, Erikson N et al (1996) Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 334:1287–1291CrossRef O’Dell JR, Haire CE, Erikson N et al (1996) Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 334:1287–1291CrossRef
54.
Zurück zum Zitat Perhala RS, Wilke WS, Clough JD, Segal AM (1991) Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate. Arthritis Rheum 34:146–152CrossRefPubMed Perhala RS, Wilke WS, Clough JD, Segal AM (1991) Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with methotrexate versus those not treated with methotrexate. Arthritis Rheum 34:146–152CrossRefPubMed
55.
Zurück zum Zitat Pincus T, Marcum SB, Callahan LF (1992) Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol 19:1885–1894PubMed Pincus T, Marcum SB, Callahan LF (1992) Longterm drug therapy for rheumatoid arthritis in seven rheumatology private practices: II. Second line drugs and prednisone. J Rheumatol 19:1885–1894PubMed
56.
Zurück zum Zitat Pope JE, Bellamy N, Seibold JR et al (2001) A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 44:1351–1358CrossRefPubMed Pope JE, Bellamy N, Seibold JR et al (2001) A randomized, controlled trial of methotrexate versus placebo in early diffuse scleroderma. Arthritis Rheum 44:1351–1358CrossRefPubMed
57.
Zurück zum Zitat Prey S, Paul C (2009) Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. Br J Dermatol 160:622–628CrossRefPubMed Prey S, Paul C (2009) Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. Br J Dermatol 160:622–628CrossRefPubMed
58.
Zurück zum Zitat Ramanan AV, Campbell-Webster N, Ota S et al (2005) The effectiveness of treating juvenile dermatomyositis with methotrexate and aggressively tapered corticosteroids. Arthritis Rheum 52:3570–3578CrossRefPubMed Ramanan AV, Campbell-Webster N, Ota S et al (2005) The effectiveness of treating juvenile dermatomyositis with methotrexate and aggressively tapered corticosteroids. Arthritis Rheum 52:3570–3578CrossRefPubMed
59.
Zurück zum Zitat Ranganathan P (2008) An update on methotrexate pharmacogenetics in rheumatoid arthritis. Pharmacogenomics 9:439–451CrossRefPubMed Ranganathan P (2008) An update on methotrexate pharmacogenetics in rheumatoid arthritis. Pharmacogenomics 9:439–451CrossRefPubMed
60.
Zurück zum Zitat Rau R (2007) Das Methotrexat-Buch – Aktuelle Therapiekonzepte in der Rheumatologie und Dermatologie. UNI-MED, Bremen Rau R (2007) Das Methotrexat-Buch – Aktuelle Therapiekonzepte in der Rheumatologie und Dermatologie. UNI-MED, Bremen
61.
Zurück zum Zitat Rau R, Herborn G, Karger T, Werdier D (1991) Retardation of radiologic progression in rheumatoid arthritis with methotrexate therapy. A controlled study. Arthritis Rheum 34:1236–1244CrossRefPubMed Rau R, Herborn G, Karger T, Werdier D (1991) Retardation of radiologic progression in rheumatoid arthritis with methotrexate therapy. A controlled study. Arthritis Rheum 34:1236–1244CrossRefPubMed
62.
Zurück zum Zitat Rau R, Herborn G, Menninger H, Sangha O (1998) Progression in early erosive rheumatoid arthritis: 12 month results from a randomized controlled trial comparing methotrexate and gold sodium thiomalate. Br J Rheumatol 37:1220–1226CrossRefPubMed Rau R, Herborn G, Menninger H, Sangha O (1998) Progression in early erosive rheumatoid arthritis: 12 month results from a randomized controlled trial comparing methotrexate and gold sodium thiomalate. Br J Rheumatol 37:1220–1226CrossRefPubMed
63.
Zurück zum Zitat Rau R, Schleusser B, Herborn G, Karger T (1997) Long-term treatment of destructive rheumatoid arthritis with methotrexate. J Rheumatol 24:1881–1889PubMed Rau R, Schleusser B, Herborn G, Karger T (1997) Long-term treatment of destructive rheumatoid arthritis with methotrexate. J Rheumatol 24:1881–1889PubMed
64.
Zurück zum Zitat Reiss AB, Carsons SE, Anwar K et al (2008) Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum 58:3675–3683CrossRefPubMed Reiss AB, Carsons SE, Anwar K et al (2008) Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum 58:3675–3683CrossRefPubMed
65.
Zurück zum Zitat Salliot C, van der HD (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68: 1100–1104CrossRefPubMed Salliot C, van der HD (2009) Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 68: 1100–1104CrossRefPubMed
66.
Zurück zum Zitat Schneider M, Lelgemann M, Abholz HH et al (2005) Interdisziplinäre Leitlinie – Management der frühen Arthritis. Steinkopff, Darmstadt Schneider M, Lelgemann M, Abholz HH et al (2005) Interdisziplinäre Leitlinie – Management der frühen Arthritis. Steinkopff, Darmstadt
67.
Zurück zum Zitat Skopouli FN, Jagiello P, Tsifetaki N, Moutsopoulos HM (1996) Methotrexate in primary Sjogren’s syndrome. Clin Exp Rheumatol 14:555–558PubMed Skopouli FN, Jagiello P, Tsifetaki N, Moutsopoulos HM (1996) Methotrexate in primary Sjogren’s syndrome. Clin Exp Rheumatol 14:555–558PubMed
68.
Zurück zum Zitat Sokka T, Kautiainen H, Toloza S et al (2007) QUEST-RA quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries. Ann Rheum Dis 66:1491–1496CrossRefPubMed Sokka T, Kautiainen H, Toloza S et al (2007) QUEST-RA quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries. Ann Rheum Dis 66:1491–1496CrossRefPubMed
69.
Zurück zum Zitat Spiera RF, Mitnick HJ, Kupersmith M et al (2001) A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA). Clin Exp Rheumatol 19:495–501PubMed Spiera RF, Mitnick HJ, Kupersmith M et al (2001) A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA). Clin Exp Rheumatol 19:495–501PubMed
70.
Zurück zum Zitat Tarner IH, Manger B, Fleck M et al (2009) Evidenzbasierte Empfehlungen einer nationalen Expertenrunde zum Einsatz von Methotrexat bei entzündlich-rheumatischen Erkrankungen. Akt Rheumatol (Epub) Tarner IH, Manger B, Fleck M et al (2009) Evidenzbasierte Empfehlungen einer nationalen Expertenrunde zum Einsatz von Methotrexat bei entzündlich-rheumatischen Erkrankungen. Akt Rheumatol (Epub)
71.
Zurück zum Zitat Thompson RN, Watts C, Edelman J et al (1984) A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 11:760–763PubMed Thompson RN, Watts C, Edelman J et al (1984) A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis. J Rheumatol 11:760–763PubMed
72.
Zurück zum Zitat Tugwell P, Pincus T, Yocum D et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group. N Engl J Med 333:137–141CrossRefPubMed Tugwell P, Pincus T, Yocum D et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group. N Engl J Med 333:137–141CrossRefPubMed
73.
Zurück zum Zitat van den Hoogen FH, Boerbooms AM, Swaak AJ et al (1996) Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 35:364–372CrossRef van den Hoogen FH, Boerbooms AM, Swaak AJ et al (1996) Comparison of methotrexate with placebo in the treatment of systemic sclerosis: a 24 week randomized double-blind trial, followed by a 24 week observational trial. Br J Rheumatol 35:364–372CrossRef
74.
Zurück zum Zitat van der Heijde DM, Oerlemans R, Dijkmans B et al (2009) Folate receptor-ß as potential delivery route for novel folate antagonists to macrophages in synovial tissue of rheumatoid arthritis patients. Arthritis Rheum 60:12–21CrossRef van der Heijde DM, Oerlemans R, Dijkmans B et al (2009) Folate receptor-ß as potential delivery route for novel folate antagonists to macrophages in synovial tissue of rheumatoid arthritis patients. Arthritis Rheum 60:12–21CrossRef
75.
Zurück zum Zitat van DH, van AJ, Lard LR et al (2007) Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 56:1424–1432CrossRef van DH, van AJ, Lard LR et al (2007) Efficacy of methotrexate treatment in patients with probable rheumatoid arthritis: a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 56:1424–1432CrossRef
76.
Zurück zum Zitat van Ede AE, Laan RF, Rood MJ et al (2001) Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 44:1515–1524CrossRef van Ede AE, Laan RF, Rood MJ et al (2001) Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum 44:1515–1524CrossRef
77.
Zurück zum Zitat Vencovsky J, Jarosova K, Machacek S et al (2000) Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis. Scand J Rheumatol 29:95–102CrossRefPubMed Vencovsky J, Jarosova K, Machacek S et al (2000) Cyclosporine A versus methotrexate in the treatment of polymyositis and dermatomyositis. Scand J Rheumatol 29:95–102CrossRefPubMed
78.
Zurück zum Zitat Weinblatt ME, Coblyn JS, Fox DA et al (1985) Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 312:818–822PubMedCrossRef Weinblatt ME, Coblyn JS, Fox DA et al (1985) Efficacy of low-dose methotrexate in rheumatoid arthritis. N Engl J Med 312:818–822PubMedCrossRef
79.
Zurück zum Zitat Weisman MH, Furst DE, Park GS et al (2006) Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis. Arthritis Rheum 54:607–612CrossRefPubMed Weisman MH, Furst DE, Park GS et al (2006) Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis. Arthritis Rheum 54:607–612CrossRefPubMed
80.
Zurück zum Zitat Wessels JA, Huizinga TW, Guchelaar HJ (2008) Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology (Oxford) 47:249–255 Wessels JA, Huizinga TW, Guchelaar HJ (2008) Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology (Oxford) 47:249–255
81.
Zurück zum Zitat Wilke WS, Calabrese LH, Scherbel AL (1980) Methotrexate in the treatment of rheumatoid arthritis; pilot study. Cleve Clin Q 47:305–309PubMed Wilke WS, Calabrese LH, Scherbel AL (1980) Methotrexate in the treatment of rheumatoid arthritis; pilot study. Cleve Clin Q 47:305–309PubMed
82.
Zurück zum Zitat Williams HJ, Willkens RF, Samuelson CO et al (1985) Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 28:721–730CrossRefPubMed Williams HJ, Willkens RF, Samuelson CO et al (1985) Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 28:721–730CrossRefPubMed
83.
Zurück zum Zitat Willkens RF, Watson MA, Paxson CS (1980) Low dose pulse methotrexate therapy in rheumatoid arthritis. J Rheumatol 7:501–505PubMed Willkens RF, Watson MA, Paxson CS (1980) Low dose pulse methotrexate therapy in rheumatoid arthritis. J Rheumatol 7:501–505PubMed
84.
Zurück zum Zitat Willkens RF, Williams HJ, Ward JR et al (1984) Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Arthritis Rheum 27:376–381CrossRefPubMed Willkens RF, Williams HJ, Ward JR et al (1984) Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Arthritis Rheum 27:376–381CrossRefPubMed
85.
Zurück zum Zitat Wolfe F, Cathey MA (1991) The effect of age on methotrexate efficacy and toxicity. J Rheumatol 18:973–977PubMed Wolfe F, Cathey MA (1991) The effect of age on methotrexate efficacy and toxicity. J Rheumatol 18:973–977PubMed
86.
Zurück zum Zitat Wunder A, Muller-Ladner U, Stelzer EHK et al (2003) Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. J Immunol 170:4793–4803PubMed Wunder A, Muller-Ladner U, Stelzer EHK et al (2003) Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. J Immunol 170:4793–4803PubMed
Metadaten
Titel
Methotrexat in der Rheumatologie
verfasst von
Prof. Dr. C. Fiehn
Publikationsdatum
01.11.2009
Verlag
Springer-Verlag
Erschienen in
Zeitschrift für Rheumatologie / Ausgabe 9/2009
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI
https://doi.org/10.1007/s00393-009-0535-2

Kompaktes Leitlinien-Wissen Innere Medizin (Link öffnet in neuem Fenster)

Mit medbee Pocketcards schnell und sicher entscheiden.
Leitlinien-Wissen kostenlos und immer griffbereit auf ihrem Desktop, Handy oder Tablet.

Neu im Fachgebiet Innere Medizin

Vorhofflimmern: Antikoagulation vor Schlaganfall von Vorteil

Erleiden Menschen mit Vorhofflimmern einen ischämischen Schlaganfall, ist dieser weniger schwer, auch sind Infarktgröße und Blutungsrisiko geringer, wenn sie zuvor orale Antikoagulanzien erhalten haben. Die Art der Antikoagulation spielt dabei keine Rolle.

Frühe CLL-Therapie: BTK-Hemmer verlängert EFS und PFS, aber nicht OS

Auch nach sechs Jahren ergibt sich kein Überlebensvorteil einer Therapie mit dem BTK-Hemmer Ibrutinib für Menschen mit frühem CLL-Stadium und erhöhtem Progressionsrisiko. Die Progressionsrate wird mit der Behandlung jedoch um über 80% gesenkt.

Mehr Cholesterin im Essen = höheres Herzinfarktrisiko

Je mehr Cholesterin man täglich über die Nahrung zu sich nimmt, desto höher ist offenbar das Herzinfarktrisiko – das legt eine Studie mit US-Veteranen zumindest für Männer nahe.

Antikoagulation bei Vorhofflimmern: Sind DOAK noch zu toppen?

Gegen Thromboembolien so wirksam wie ein DOAK, bei zugleich geringerem Blutungsrisiko – werden Faktor-XI-Hemmer als neue Antikoagulanzien dieser Erwartung gerecht? Eine aktuell publizierte Vergleichsstudie gibt darüber Aufschluss.

EKG Essentials: EKG befunden mit System (Link öffnet in neuem Fenster)

In diesem CME-Kurs können Sie Ihr Wissen zur EKG-Befundung anhand von zwölf Video-Tutorials auffrischen und 10 CME-Punkte sammeln.
Praxisnah, relevant und mit vielen Tipps & Tricks vom Profi.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.